1. Technical Field of the Invention
The present invention relates to novel cosmetic/pharmaceutical compositions comprising at least one .beta.-adrenergic agonist as a substance P antagonist, more particularly dermatological compositions, for the treatment of disorders associated with an excess in the synthesis and/or in the release of substance P.
This invention also relates to novel cosmetic/pharmaceutical compositions for topical application comprising at least one .beta.-adrenergic agonist.
Too, this invention relates to a cosmetic/pharmaceutical treatment regime or regimen for decreasing the pain related to an excess in the synthesis and/or in the release of substance P, or for decreasing the irritant effect of a normally irritating compound, according to which a composition comprising at least one .beta.-adrenergic agonist is topically applied onto the skin, onto the hair and/or onto the mucous membranes.
2. Description of the Prior Art
There exist in mammals polypeptides belonging to the family of tachykinins which induce rapid contractions with respect to smooth muscle fibers. Exemplary compounds of this family include neurokinin .beta., neurokinin .alpha. and substance P.
Substance P is a polypeptide (undecapeptide) chemical species developed and released by a nerve ending. Localization of substance P is specific to neurones, both in the central nervous system and in the organs at the periphery. Thus, a great many organs or tissues receive neurone afferences containing substance P, in particular the salivary glands, the stomach, the pancreas, the intestines (in the latter, the distribution of substance P is superimposed on Meissner's and Auerbach's intrinsic nerve plexus), the cardiovascular system, the thyroid gland, the skin, the iris and ciliary bodies, the bladder and, very obviously, the peripheral and central nervous systems.
Because of the ubiquitous distribution of substance P, a great many disorders are associated with an excess in the synthesis and/or in the release of substance P.
Substance P is involved, in particular, in the transmission of pain and in diseases of the central nervous system (for example anxiety, psychoses, neuropathies, neurodegenerative disorders of Alzheimer's senile dementia type, AIDS-related dementia, Parkinson's disease, Down's syndrome, Korsakoff's syndrome, multiple scleroses or schizophrenia), in respiratory diseases (such as, for example, bronchopneumonia) and inflammatory diseases (such as, for example, rheumatoid polyarthritis), in allergic syndromes (such as, for example, asthma, allergic rhinitis, allergic pharyngitis, urticaria or eczematous dermatitides), in gastrointestinal diseases (such as, for example, ulcers, colitis or Crohn's disease), in cutaneous disorders (such as, for example, psoriasis, pruriginous diseases, herpes, photodermatoses, atopic dermatitides, contact dermatitides, lichens, prurigo, pruritus, erythemas, in particular sunburn, or insect stings), in fibroses and other disorders of maturation of collagens (such as, for example, scleroderma), in cardiovascular disorders, in vasospastic disorders (such as, for example, migraines or Raynaud's disease), in immunological disorders, in disorders of the urinary tract (such as, for example, incontinence or cystitis), in rheumatic diseases, in certain dermatological diseases and in ophthalmological conditions (such as, for example, conjunctivitis, uveitides, ocular pruritus, ocular pains or irritations).
The administration of a substance P antagonist is one of the effective therapeutic alternatives in all of the conditions and afflictions indicated above.
By "substance P antagonist" is intended any compound capable of partially or indeed completely inhibiting the biological effect of substance P. In particular, for a substance to be recognized as a substance P antagonist, it must induce a coherent pharmacological response (including or not including its binding to the substance P receptor), in particular in one of the following tests:
(a) the antagonist substance must decrease the extravasation of the plasma through the vascular wall induced by capsaicin or by an antidromic nerve stimulation, or, alternatively; PA1 (b) the antagonist substance must cause inhibition of the contraction of the smooth muscles induced by the administration of substance P. PA1 (1) agents which modulate cutaneous pigmentation and/or proliferation and/or differentiation, such as retinoic acid and isomers thereof, retinol and esters thereof, vitamin D and derivatives thereof, oestrogens, such as estradiol, kojic acid or hydroquinone; PA1 (2) antibacterials, such as clindamycin phosphate, erythromycin or antibiotics from the tetracycline class; PA1 (3) agents for combating parasites, in particular metronidazole, crotamiton or pyrethroids; PA1 (4) antifungals, in particular compounds belonging to the imidazole class, such as econazole, ketoconazole or miconazole or salts thereof, polyene compounds, such as amphotericin B, compounds of the allylamine family, such as terbinafine, or octopirox; PA1 (5) antiviral agents, such as acyclovir; PA1 (6) steroidal anti-inflammatory agents, such as hydrocortisone, betamethasone valerate or clobetasol propionate, or non-steroidal anti-inflammatory agents, such as ibuprofen and salts thereof, diclofenac and salts thereof, acetylsalicylic acid, acetaminophen or glycyrrhetinic acid; PA1 (7) anaesthetic agents, such as lidocaine hydrochloride and derivatives thereof; PA1 (8) antipruriginous agents, such as thenaldine, trimeprazine or cyproheptadine; PA1 (9) keratolytic agents, such as .alpha.- and .beta.-hydroxycarboxylic acids or .beta.-ketocarboxylic acids, their salts, amides or esters and, more particularly, hydroxy acids, such as glycolic acid, lactic acid, salicylic acid, citric acid and, generally, the fruit acids, and 5-(n-octanoyl)salicylic acid; PA1 (10) agents for combating free radicals, such as .alpha.-tocopherol or esters thereof, superoxide dismutases, certain metal chelating agents or ascorbic acid and esters thereof; PA1 (11) antiseborrhoeics, such as progesterone; PA1 (12) antidandruff agents, such as octopirox or zinc pyrithione; PA1 (13) antiacne agents, such as retinoic acid or benzoyl peroxide.
To date, substance P antagonists are administered to treat the disorders indicated above.